Objective: To investigate the safety and reliability of using high-frequency electric welding device (HFWD) for arterial closure. Methods: Six Tibetan minipigs were equally randomized into HFWD group and harmonic scalpel group (HS group). Under general anesthesia, carotid and femoral arteries of the pigs were isolated and skeletonized, and were then closed and divided using HFWD or HS, respectively. The bursting pressure of the vessels after sealing, sealing time, maximum temperature during sealing and the pathological injuries in the sealing area were compared between the two groups. Results: In all vessels without distinction of diameter, the average burst pressure after sealing in HFWD group was significantly higher than that in HS group (489.64 mmHg vs. 439.88 mmHg, P<0.05); in vessels with diameter ≤3 mm, the burst pressure showed no significant difference between HFWD group and HS group (593.40 mmHg vs. 572.48 mmHg, P>0.05); in vessels with diameter either >3~5 mm or >5~7 mm, the burst pressure in HFWD group was significantly higher than that in HS group (457.02 mmHg vs. 404.32 mmHg; 418.51 mmHg vs. 342.84 mmHg, both P<0.05). No matter what the vessel diameter was, the sealing time in HFWD group was significantly shorter than that in HS group (all P<0.05). The average maximum temperature during sealing in HFWD group was significantly lower than that in HS group (65.91 ℃ vs. 105.25 ℃, P<0.05). The collagen denaturation and smooth muscle injury in vascular wall of the sealing site were milder in HFWD group than those in HS group. Conclusion: Using HFWD for arterial closure is safe and reliable.